Spatial Training Attenuates Long-Term Alzheimer’s Disease-Related Pathogenic Processes in APP/PS1 Mice

Article type: Research Article

Authors: Zhao, Yang^{a; b; 1} | Bao, Jian^{b; c; 1} | Liu, Wei^{b; c} | Gong, Xiaokang^b | Liang, Zheng^b | Li, Wenshuang^b | Wu, Mengjuan^{b; c} | Xiao, Yifan^{b; c} | Sun, Binlian^b | Wang, Xiaochuan^d | Wang, Jian-Zhi^d | Wang, Jun^{a; *} | Shu, Xiji^{b; c; *}

Affiliations: [a] International Joint Research Center for General Health, Precision Medicine & Nutrition, Hubei University of Technology, Wuhan, China | [b] Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan China | [c] Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, China | [d] Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Correspondence: [*] Correspondence to: Xiji Shu, Institutes of Biomedical Sciences, Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, China. Tel.: +86 18971625295; E-mail: [email protected] and Jun Wang, International Joint Research Center for General Health, Precision Medicine & Nutrition, Hubei University of Technology, Wuhan, China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Alzheimer’s disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-β (Aβ) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aβ deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated. Objective:To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice. Methods:We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence. Results:One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aβ deposition and decrease the expression of β-secretase (BACE1) and amyloid-β protein precursor (AβPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage. Conclusion:Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.

Keywords: Adult hippocampal neurogenesis, Alzheimer’s disease, amyloid-β , AβPP, BACE1, spatial training

DOI: 10.3233/JAD-215016

Journal: Journal of Alzheimer's Disease, vol. 85, no. 4, pp. 1453-1466, 2022